This project is a continuation of our long-term study on the cellular and molecular mechanisms of normal and neoplastic T and B lymphocyte maturation. Our first goal is to study differentiation of T lymphocytes, with a major focus on analyzing the number and type of lineages beginning in the bone marrow and ending in peripheral immunocompetent T cell pools. Another aspect of normal T cell maturation is the analysis of how thymic epithelial cells create a microenvironment for the selection and/or maturation of immunocompetent T cell subsets. Immunochemical and molecular biological experiments are planned to elucidate the characteristics of T cell receptors and the genes coding for these receptors. A novel hypothesis tested in this grant is that neoplastic transformation of T lymphocytes by murine leukemia viruses is limited to that subset of T cells having antigen-specific receptors for envelope glycoproteins of these viruses. We shall test this notion by using various immunochemical reagents to define virus receptors and antigen-specific T cell receptors for these viral envelope glycoproteins. In a third line of work we shall examine another class of T cell receptors involved in the homing and organization of lymphoid tissues in normal hosts, and the metastasis of lymphomas in tumor bearing hosts. We are referring to lymphocyte receptors for particular blood vessels which govern the homing of lymphocytes to various parts of the body, and our analysis includes a biological and a biochemical characterization of these receptors. Finally, we shall look closely at normal and neoplastic B cell maturation, with special emphasis on studying isotypes as markers of B cell maturational lineages, and the organization of heavy chain constant and variable region genes during this maturation in both normal and neoplastic B cells.